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β-cell transplantation for diabetes therapy

2008; Elsevier BV; Volume: 372; Issue: 9632 Linguagem: Inglês

10.1016/s0140-6736(08)60984-8

1474-547X

Camillo Ricordi, Berhard J Hering, AM James Shapiro,

Diabetes and associated disorders

Piero Ruggenenti and colleagues (March 15, p 883)1Ruggenenti P Remuzzi A Remuzzi G Decision time for pancreatic islet-cell transplantation.Lancet. 2008; 371: 883-884Summary Full Text Full Text PDF PubMed Scopus (24) Google Scholar highlight their failure to establish a clinical islet transplantation programme. Results of islet transplantation are similar to those of the early days of organ transplantation, where initial success rarely met with long-term function.2Ricordi C Strom T Clinical islet transplantation: advances and immunological challenges.Nat Rev Immunol. 2004; 4: 259-268Crossref PubMed Scopus (323) Google Scholar The Edmonton protocol achieved reproducible insulin independence after islet transplantation,3Shapiro AM Ricordi C Hering BJ et al.International multicenter trial of islet transplantation in type 1 diabetes using the Edmonton protocol.N Engl J Med. 2006; 355: 1318-1330Crossref PubMed Scopus (1584) Google Scholar with more than 80% of recipients still insulin-free at 1 year. Differences in outcome among centres3Shapiro AM Ricordi C Hering BJ et al.International multicenter trial of islet transplantation in type 1 diabetes using the Edmonton protocol.N Engl J Med. 2006; 355: 1318-1330Crossref PubMed Scopus (1584) Google Scholar illustrate the complexity of the procedure and its immunological challenges.2Ricordi C Strom T Clinical islet transplantation: advances and immunological challenges.Nat Rev Immunol. 2004; 4: 259-268Crossref PubMed Scopus (323) Google Scholar New challenges include factors affecting long-term islet function, including mass attrition possibly related to impaired β-cell regeneration4Hering BJ Kandaswamy R Ansite JD et al.Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes.JAMA. 2005; 293: 830-835Crossref PubMed Scopus (496) Google Scholar under the immunosuppression previously used in successful islet transplantation.3Shapiro AM Ricordi C Hering BJ et al.International multicenter trial of islet transplantation in type 1 diabetes using the Edmonton protocol.N Engl J Med. 2006; 355: 1318-1330Crossref PubMed Scopus (1584) Google Scholar Despite the slow decline in islet function seen over the years, recipients maintained near-normal glycosylated haemoglobin and were protected from severe hypoglycaemia. Additionally, improved results with single-donor islet transplantation have been reported,4Hering BJ Kandaswamy R Ansite JD et al.Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes.JAMA. 2005; 293: 830-835Crossref PubMed Scopus (496) Google Scholar, 5Hering BJ Parkey J Kandaswamy R et al.Long-term survival of human islet allografts in type 1 diabetes.Am J Transplant. 2007; 7: 205Google Scholar with longer follow-up studies indicating 4-year insulin-independence rates exceeding 50%.5Hering BJ Parkey J Kandaswamy R et al.Long-term survival of human islet allografts in type 1 diabetes.Am J Transplant. 2007; 7: 205Google Scholar Islet transplantation outcomes are likely to improve substantially over the next 3–5 years, as a result of novel immunosuppressive regimens with fewer toxic effects. Even more far-reaching improvements will emerge from islet processing, alternative islet sources, cellular immunotherapeutics, tissue engineering, implantation techniques and sites, bioimaging, and post-transplant β-cell monitoring. Islet transplantation will provide the platform for the next generation of cellular therapeutics for β-cell replacement as a curative therapy for diabetes. Sceptics and critics can be anticipated at each turn, yet the incalculable value of a curative therapy and encouraging signs of progress make a decision to move forward an easy one. The Clinical Islet Transplantation Consortium: Camillo Ricordi, A M James Shapiro, James Markmann, Christian P Larsen, Dixon Kaufman, Peter Stock, Olle Korsgren, José Oberholzer, Ali Naji, Bernhard J Hering. We declare that we have no conflict of interest. β-cell transplantation for diabetes therapy – Authors' replyIn the largest series of islet transplant recipients treated with a common protocol of islet preparation and post-transplantation care (the Edmonton protocol), only 16 of 36 patients were still insulin-independent at 1 year; 10 had complete graft loss.1 Consistently, comparative studies have found that only 31% of islet recipients versus 96% of whole-pancreas recipients were insulin-free 1 year after transplantation.2 Full-Text PDF